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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tmem178tm1Lex
targeted mutation 1, Lexicon Pharmaceuticals
MGI:5007374
Summary 1 genotype
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Tmem178tm1Lex/Tmem178tm1Lex involves: 129S5/SvEvBrd * C57BL/6 MGI:5804664


Genotype
MGI:5804664
hm1
Allelic
Composition
Tmem178tm1Lex/Tmem178tm1Lex
Genetic
Background
involves: 129S5/SvEvBrd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tmem178tm1Lex mutation (2 available); any Tmem178 mutation (13 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Trabecular thinning and increase in osteoclast surface normalized to bone surface in Tmem178tm1Lex/Tmem178tm1Lex mice

skeleton
• mutant bone marrow macrophages (BMMs) isolated from 6- to 8-wk-old mice and cultured with M-CSF and RANKL for 3-5 days display enhanced osteoclast differentiation relative to wild-type controls
• increased osteoclastogenesis is also noted in the co-culture system with either wild-type or mutant bone marrow stromal cells
• following addition of TNF or LPS, in vitro osteoclast differentiation is significantly increased, as quantified by the number of TRAP+ osteoclasts
• at 16 weeks of age, females show a significant increase in the % of osteoclast surface per bone surface (% OcS/BS) in TRAP-stained femurs relative to wild-type controls
• following supracalvarial LPS injection, mice show a significantly higher % OcS/BS than wild-type controls
• in the K/BXN serum-transfer arthritis model, mice exhibit a significantly higher % OcS/BS in the knee bone than wild-type controls
• however, osteoblast numbers, mineral apposition rate (MAR), and bone formation rate (BFR) are normal under basal conditions
• mutant pre-osteoclasts (BMMs cultured with M-CSF and RANKL for 24 hours) exhibit higher levels of intracellular Ca2+ with fluxes of greater amplitude relative to wild-type controls
• in the K/BXN serum-transfer arthritis model, mice exhibit a normal inflammatory response, as measured by hind paw swelling, but show significantly more inflammatory bone loss than wild-type controls, as determined by the reduction in remaining knee bone volume and increased % OcS/BS
• mice develop osteopenia under basal conditions
• at 16 weeks of age, females show a 35% decrease in trabecular bone volume per tissue volume in proximal femurs relative to wild-type controls
• at 16 weeks of age, females show significant trabecular thinning in proximal femurs relative to wild-type controls
• at 16 weeks of age, females show decreased bone mass under basal conditions
• mutant BMMs cultured on bovine bone slices in the presence of M-CSF and RANKL for 10 days show a significant increase in % resorbed area relative to wild-type controls
• following supracalvarial LPS injection, mice develop marked focal osteolysis and increased osteoclast surface relative to wild-type controls
• however, the resorptive capacity of individual osteoclasts is not altered, as determined by plating committed osteoclasts (BMMs differentiated on plastic with M-CSF and RANKL for 3 days) on bovine bone slices for 48 hours

immune system
• mutant bone marrow macrophages (BMMs) isolated from 6- to 8-wk-old mice and cultured with M-CSF and RANKL for 3-5 days display enhanced osteoclast differentiation relative to wild-type controls
• increased osteoclastogenesis is also noted in the co-culture system with either wild-type or mutant bone marrow stromal cells
• following addition of TNF or LPS, in vitro osteoclast differentiation is significantly increased, as quantified by the number of TRAP+ osteoclasts
• at 16 weeks of age, females show a significant increase in the % of osteoclast surface per bone surface (% OcS/BS) in TRAP-stained femurs relative to wild-type controls
• following supracalvarial LPS injection, mice show a significantly higher % OcS/BS than wild-type controls
• in the K/BXN serum-transfer arthritis model, mice exhibit a significantly higher % OcS/BS in the knee bone than wild-type controls
• however, osteoblast numbers, mineral apposition rate (MAR), and bone formation rate (BFR) are normal under basal conditions
• mutant pre-osteoclasts (BMMs cultured with M-CSF and RANKL for 24 hours) exhibit higher levels of intracellular Ca2+ with fluxes of greater amplitude relative to wild-type controls
• in the K/BXN serum-transfer arthritis model, mice exhibit a normal inflammatory response, as measured by hind paw swelling, but show significantly more inflammatory bone loss than wild-type controls, as determined by the reduction in remaining knee bone volume and increased % OcS/BS

hematopoietic system
• mutant bone marrow macrophages (BMMs) isolated from 6- to 8-wk-old mice and cultured with M-CSF and RANKL for 3-5 days display enhanced osteoclast differentiation relative to wild-type controls
• increased osteoclastogenesis is also noted in the co-culture system with either wild-type or mutant bone marrow stromal cells
• following addition of TNF or LPS, in vitro osteoclast differentiation is significantly increased, as quantified by the number of TRAP+ osteoclasts
• at 16 weeks of age, females show a significant increase in the % of osteoclast surface per bone surface (% OcS/BS) in TRAP-stained femurs relative to wild-type controls
• following supracalvarial LPS injection, mice show a significantly higher % OcS/BS than wild-type controls
• in the K/BXN serum-transfer arthritis model, mice exhibit a significantly higher % OcS/BS in the knee bone than wild-type controls
• however, osteoblast numbers, mineral apposition rate (MAR), and bone formation rate (BFR) are normal under basal conditions
• mutant pre-osteoclasts (BMMs cultured with M-CSF and RANKL for 24 hours) exhibit higher levels of intracellular Ca2+ with fluxes of greater amplitude relative to wild-type controls

cellular
• mutant bone marrow macrophages (BMMs) isolated from 6- to 8-wk-old mice and cultured with M-CSF and RANKL for 3-5 days display enhanced osteoclast differentiation relative to wild-type controls
• increased osteoclastogenesis is also noted in the co-culture system with either wild-type or mutant bone marrow stromal cells
• following addition of TNF or LPS, in vitro osteoclast differentiation is significantly increased, as quantified by the number of TRAP+ osteoclasts





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last database update
11/12/2024
MGI 6.24
The Jackson Laboratory